Saturated free fatty acid is believed to be a major factor in the development of fatty liver. Palmitic acid, major saturated fatty acid, induces cell apoptosis in various tissues. Mitogen activated protein kinases (MAPKs) such as c-Jun NH2-terminal kinases (JNKs) and p38 MAPK are attractive targets for treatment of fatty liver. Thus, we examined the effect of palmitic acid on apoptosis and its relationship between JNK and p38 MAPK in primary cultured pig hepatocytes. In the present study, palmitic acid decreased cell viability of hepatocytes in a dose-dependent manner. Indeed, palmitic acid decreased Bcl-2 expression but increased Bax expression in pig hepatocytes, which was blocked by the treatment of SP600125 (a JNK inhibitor) and SB203580 (a p38 MAPK inhibitor). Western immunoblotting analysis also revealed that palmitic acid increased JNK and p38 MAPK in a time-dependent manner. In conclusion, palmitic acid induced apoptosis via JNK and p38 MAPK activation in primary cultured pig hepatocytes. Key words: Pig hepatocyte, palmitic acid, apoptosis, JNK, p38 MAPK Received 19 August 2008; Revised version received 2 September 2008; Accepted 3 September 2008