Treatment of patients with chronic hepatitis C with the current standard pegylated interferon (PEG-IFN) and ribavirin achieves overall response (SVR) rates of ~55%. A role of CD4+ CD25+ regulatory T cells (Treg cells) has been proposed as they can suppress HCV-specific T cells in HCV-infected patients. Patients with chronic HCV legible for PEG-IFN plus ribavirin treatment, were classified according to their response to treatment into two groups (responders and nonresponders, 32 and 27 patients respectively). Blood and plasma samples were collected at the start of treatment and at 12 and 24 weeks during treatment. Immunophenotyping by flow cytometry for Treg cells, the FOXP-3 expression using real-time PCR and measurement of IL-10, TGF-β CXCL-9 and CXCL-10 were performed. Increased expression of Treg cells was detected in patients who didn't respond to treatment before and during treatment. Also, the levels of IL- 10, TGF-β, CXCL-9 and CXCL-10 revealed significant increase in non-responders all through compared to responders group. Evaluation of Treg cells, cytokines (IL-10 & TGF-β) and chemokines (CXCL-9 & CXCL-10) before starting the treatment could be a predictor of response to treatment with PEG-IFN plus ribavirin. The optimum levels which would differentiate between responders and non-responders are needed to be defined before- hand.