Background The aim of this study was to determine whether leptin and insulin resistance (IR) showed differences between steatotic patients with and without elevated serum transaminases. Methods. The study included 32 patients with fatty liver and high serum transaminase level (group I), 31 patients with fatty liver and normal serum transaminase level (group II), and 8 nonobese and nonsteatotic controls. The presence of steatosis was demonstrated by ultrasonography. Due to the effect of body mass index (BMI) on leptin levels, groups I and II were divided to form four subgroups for analysis (group IA, BMI less than or equal to30; group IIB, BMI >30; group IIA, BMI less than or equal to30; and group IIB, BMI > 30. Results. The serum leptin levels in group IIB were significantly higher than the levels in group IB (P = 0.017). Serum leptin was also higher in group IIA than in group IA, but this difference was not statistically significant (P = 0.097). Logistic regression analysis revealed a significant negative correlation between serum leptin level and the presence of a high transaminase level (odds ratio, 0.97; 95% confidence interval, 0.95-0.99). The levels of IR in the four patient groups were comparable, but the controls had significantly lower IR levels than group IIA. Conclusions. Elevated serum leptin seems to be a feature of steatotic patients with normal transaminase levels, and the level of serum leptin seems to decrease as the hepatocyte injury develops. IR is a common feature of fatty liver disease, irrespective of the presence of hepatocellular necrosis.