Background: Insulin resistance plays an important role in pathogenesis of NAFLD. Adiponectin has antilipogenic and anti-inflammatory effects, while TNF-α reduces insulin sensitivity and has proinflammatory effects. The aims of this study are to determine the efficacy and safety of pentoxifylline, a TNF-α inhibitor, compare with placeboMethods: Thirty-two patients had biopsy-confirmed NASH and NAFLD with other causes of liver disease and secondary causes of NASH excluded. All patients had persistently elevated ALT (>1.5 times for more than 6 months, after dietary treatment for 2 months) were randomized into 2 groups. The first group was given pentoxifylline at a dosage of 400 mg t.i.d. plus dietary treatment and the second group was given placebo with dietary treatment for 6 months. The changes in ALT, AST, insulin resistance index (homeostatic metabolic assessment insulin resistance (HOMA IR) index, waist/hip ratio), TNF-α and adiponectin level from baseline to at the end of treatment were compared between 2 groups.Results: The 32 patients had a mean age of 48.9 ± 11.7 yr. Nineteen patients (59%) were male, Five patients (15.6%) were obese (BMI >30 kg/m2) with mean BMI 26.5 ± 3.2 kg/m2, Five patients (15.6%) were type II DM, twelve patients (37.5%) were hypertension and twenty seven (84.4%) were dyslipidemia. There were no baseline demographic differences between both groups. The mean changes of serum alanine, aspartate aminotransferase and fasting plasma glucose levels difference significantly from baseline in the pentoxifylline group compared to the placebo group. (ALT + 68.2 ฑ 40.7 vs. + 18.2±  34.2, p = 0.001; AST + 27.3 ± 20.4 vs. + 7.9 ±  19.8, p = 0.008; FBS + 9.1 ±  10.7 vs. - 0.7 ±  5.7, p = 0.003, respectively) The pentoxifylline groups showed more improvement in BMI, waist/hip ratio and serum TNF-α, compared with the placebo groups, without any statistically significant. Adinopectin levels were not changed significantly between both groups. There was no serious adverse events occurred.Conclusions: Pentoxifylline therapy effectively achieved significant improvement in aminotransferase level among patients with NAFLD when compared to placebo.