Abstract Background Based on previous studies in experimental models, pro-inflammatory Th1 cytokines (i.e. TNF-α and IFN-γ) are thought to play a pathogenic role in hepatic ischemia/reperfusion injury, while anti-inflammatory Th2 cytokines (i.e. IL-4 and IL-10) have been associated with reduced liver disease severity. To test the relevance of these concepts in humans, cytokine expression profiles were characterized in liver biopsies from patients undergoing hepatic resection following intermittent portal clamping. Methods Twelve patients were analyzed for the intrahepatic expression of TNF-α, IFN-γ, IL-4 and IL-10 before and about 90 min after the last reperfusion. In addition, parameters of liver damage including sALT and serum levels of TNF-α were analyzed at 2, 24 and 48 h after surgery. Results When compared with pre-reperfusion liver specimens, all post-reperfusion biopsies showed significantly increased levels of TNF-α and IFN-γ mRNAs. Conversely IL-4 and IL-10 mRNA levels were significantly increased in only seven patients. A negative correlation was observed between Th2 cytokines (IL-4, IL-10) and ALT and serum levels of TNF-α. Furthermore, the presence of hepatic steatosis was significantly associated with lower intrahepatic contents of IL-4 and IL-10. Conclusions The results suggest that the local early expression of Th2 cytokines may contribute to attenuate liver injury following ischemia reperfusion in humans. The early imbalance between pro- and anti-inflammatory cytokines seen in steatotic liver subjected to I/R could explain, at least partially, the decreased tolerance of steatotic livers to I/R injury.