The cellular and humoral natural immune response induced by hepatitis C virus (HCV) is commonly unable to eradicate the virus. HCV is a highly mutable, hepatotropic RNA virus that causes acute and chronic hepatitis, an infection that involves the production of various cytokines. The aim of the study is to analyse the expression of pro-inflammatory cytokines IL-1beta, TNF-alpha, IFN-gamma and the chemokine CXCL8 (IL-8) in liver tissue and their expression and secretion in PBMC of patients with chronic hepatitis C (CHC), in response to pentoxyfilline (PTX). We studied six CHC patients, naive to treatment. Patients received PTX 400 mg twice a day/8 weeks. Pentoxyfilline resulted in decreased expression of mRNA of liver IL-1beta, TNF-alpha and IFN-gamma: 144.2 versus 83.5 molecules of IL-1beta (P < 0.05), TNF-alpha 194.3 versus 17.6 molecules (P = 0.03) and IFN-gamma 26.1 versus 0.5 molecules (P = 0.04). Following PTX, PBMC exhibited a decrease in IFN-gamma mRNA 12.2 versus 1.5 molecules (P = 0.028) and CXCL8 4.2 versus 2.5 molecules (P = 0.027). In PBMC, only the secretion of TNF-alpha was decreased 1109 versus 933.5 pg/ml, P = 0.046. Production of cytokines both locally (within the liver) and systemically (PBMC) may serve as biomarkers of the infection with hepatitis C. PTX inhibits the expression of several pro-inflammatory cytokines in the liver. These results indicate that it is worth exploring PTX in hepatitis in future clinical trials in nonresponders to antiviral treatment.