Increased insulin resistance is a therapeutic target in patients with chronic liver disease. Branched-chain amino acids (BCAA) have been reported to improve insulin resistance in in vivo experiments. Thus, we investigated the effects of BCAA on insulin resistance in patients with chronic liver disease. Twelve patients with chronic liver disease were enrolled. Each patient was given one sachet of a BCAA-enriched supplement after breakfast and another at bedtime. The effects of the BCAA-enriched supplementation on insulin resistance were examined 30, 60 and 90 days after administration by the homeostasis model assessment method for insulin resistance (HOMA-IR) and for beta cell function (HOMA-%B). The HOMA-IR and HOMA-%B values were elevated at baseline, however, these parameters showed no significant changes after administration of the BCAA-enriched supplement in the overall patient population. By stratification via gender, patients in the male group showed a significantly greater elevation in the HOMA-IR value compared to the female patients at baseline. After the administration, the HOMA-IR and HOMA-%B values were significantly decreased only in the male group (9.4+/-4.8 vs. 2.4+/-0.7, 657+/-345 vs. 126+/-36, respectively; P<0.05). We found that there was a gender difference in chronic viral liver disease-related insulin resistance. Moreover, a BCAA-enriched supplement improved insulin resistance and beta cell function in male patients with chronic viral liver disease. Thus, a BCAA-enriched supplement may be a useful therapeutic agent for decreasing insulin resistance in male patients with chronic viral liver disease.