Post-heparin plasma (PHP) lipoprotein lipase (LPL) activity and serum lipoprotein concentration were examined in Japanese Black cows affected with fat necrosis. The PHP-LPL activity in the affected cows tvas significantly (P<0.001) higher than in normal animals and tended to reduce 4 weeks after treatment with isoprothiolane. This finding indicates that affected cows have a predisposition to deposit more fat into adipose tissue than normal animals. The serum concentrations of triglyceride in beta-lipoprotein and of cholesterol, phospholipid and total lipid in alpha-lipoprotein were significantly (P<0.05) lower in the affected cows. Elevated levels of phospholipid and total lipid in alpha-lipoprotein as well as decreased levels of non-esterified fatty acid (NEFA) were observed after medication. It is suggested that isoprothiolane produces an improvement in hepatic lipid metabolism including acceleration of plasma NEFA uptake and alpha-lipoprotein secretion in affected cows.