Background Pioglitazone is effective in nonalcoholic steatohepatitis （NASH）, but the mechanisms of action are not completely understood. This study was designed to investigate the effects of pioglitazone on hepatic nuclear factor-kappa B （NF-KB） and cyclooxygenases-2 （COX-2） expression in NASH rats. Methods Thirty Sprague-Dawley male rats were randomly assigned to a control group （n=10）, NASH group （n=10）, and pioglitazone treatment group （n=10）. Liver tissues were processed for histology by hematoxylin ＆ eosin and Masson stained. Serum alanine aminotransferase （ALT）, cholesterol, triglyceride, fasting blood glucose （FBG）, fasting insulin （FINS） levels and biochemical parameters of antioxidant enzyme activities, tumor necrosis factor alpha （TNF-a）, prostaglandin E2 （PGE2） levels in serum and liver were measured. The mRNA and protein expression of peroxisome proliferator-activated receptor gamma （PPARy）, NF-KB and COX-2 were determined by real-time polymerase chain reaction, Western blotting and immunohistochemistry. One-way analysis of variance （ANOVA） and Wilcoxon＇s signed-rank test was used for the statistical analysis. Results There were severe steatosis, moderate inflammatory cellular infiltration and fibrosis in NASH rats. After pioglitazone treatment, steatosis, inflammation and fibrosis were significantly improved compared with the NASH group （X2=20.40, P 〈0.001; X2=20.17, P 〈0.001; X2=13.98, P=0.002）. Serum ALT, cholesterol, triglyceride, FBG, FINS levels were significantly elevated in the NASH group （P 〈0.05）. In the NASH group, total anti-oxidation competence （T-AOC）, superoxide dismutase （SOD）, catalase （CAT）, glutathione peroxidase （GSH-PX） and malondialdehyde （MDA） levels in serum and liver were conspicuous disordered than those parameters in the control group. Meanwhile, TNF-a and PGE2 levels in serum and liver were significantly increased compared with the control group. Immunohistochemistry showed NF-KB and C
