Pythium insidosum is the causative agent of the life threatening pythiosis. The main clinical manifestations are often found in artery (vascular type) and cornea (ocular or corneal type). Among the vascular type, thalassemia is the common underlying disease. The investigation of specific P. insidiosum antibody in serum is practical tool and provides high accuracy for diagnosis. Using the high technology, computer tomography angiogram to indicate the occlusion point in artery is another protocol that physicians often requested. However, with the high cost and availability only in tertiary care hospital are the limitation. Presently, the combination treatment, surgery, antifungal agents, and immunotherapy, has been applied since standard treatment has been established yet. Regarding the immunotherapy, 2 mg/ml protein antigen extracted from P. insidiosum (PIA) to stimulate host immune response, via subcutaneous route has been performed. The protocol is one prime dose, after diagnosis, and 6 boosters in one year period. To follow up and monitor the patients’ illnesses, the physicians investigate by observing and asking the patient directly about the lesion without any biological markers. In addition, no reliable markers regarding the patients’s previous symptom for the next visit was shown. Thus, it is dispensable to find the biological evidence base. To examine the specific antibody is to study the host immune response to the specific pathogen. Regarding the pathogen side, the presence of (13)-β-D-glucan (BG) is found in the cell wall of P. insidiosum and PIA, similar to certain kind of fungi. Therefore BG level monitoring is another attractive marker. We hypothesized that after the combination treatment, the level of both specific antibody against P. insidiosum and the BG would change and possible to apply as the monitoring surrogate markers for pythiosis. Materials and Methods The levels of BG and cytokines: IFN-γ, IL-17 in the sera prior PIA immunotherapy (PIAI) at each time point through out the 1 year regimen from vascular and corneal pythiosis patients (n=20 of each) were examined. The control sera were collected from healthy with thalassemia (n=20) and without thalassemia (n=20) for vascular pythiosis and corneal pythiosis investigation, in order. All results including the patients’ data from survivor and death groups for vascular type; visible and invisible from ocular type will be analyzed. Results All patients who survived more than 1 year after PIA immunotherapy showed the significant declining trend of serum BG (p-value<0.05) whereas the ones who died before 1 year demonstrated the high level of BG with non-significant changing (p-value<0.05) despites both group presented the non-significant difference of >423.4 picogram/ml prior PIA injection. In contrast to the cytokine level: IFN-γ and IL-17, all patients who survived more than 1 year after PIA immunotherapy showed the significant increased trend of cytokines (p-value<0.05) whereas the ones who died before 1 year demonstrated the decreased trend of cytokines’ level. Discussion The pattern of BG and cytokines: IFN-γ and IL-17 are ones of the biological markers (quantitative scale) which can be applied for the disease monitoring and prognosis. However, these biological markers have some limitation in term of their specificity. The pattern of their levels can be presented by several factors such as fungal or bacterial infection which compose of BG. Thus, the development of P. insidiosum specific biological marker for testing in parallel need to be investigated in the future.