AIM: To evaluate the effects of ethanol on the insulin- like growth factor-Ⅰ (IGF-Ⅰ) system involved in c-Jun N-terminal kinase (JNK1/2) and alcoholdehydrogenase (ADH) activity in primary cultured rat hepatocytes. METHODS: Hepatocytes isolated from male Sprague-Dawley rats were incubated with various concentrations of ethanol for different durations of time. The cells were pretreated with SP600125 (10 μmol/L) and 4-MP (200 μmol/L), and then treated with ethanol (200 mmol/L). We then measured IGF-Ⅰ secretion, IGF-Ⅰ mRNA expression, cell viability and JNK1/2 activity by radioimmunoassay, RT-PCR, MTT assay and Western blot, respectively (n = 6). RESULTS: Ethanol induced the activity of phospho (p)-JNK1/2, reaching a maximum at 60 min and then decreasing at 180 min. The effects of ethanol on the IGF-Ⅰ system were increased at 60 min (secretion: 7.11 ± 0.59 ng/mg protein vs 4.91 ± 0.51 ng/mg, mRNA expression: 150.2% ± 10.2% vs 101.5% ± 11.3%, P = 0.045) and then decreased at 180 min (secretion: 3.89 ± 0.25 ng/mg vs 5.4 ± 0.54 ng/mg protein; mRNA expression: 41.5% ± 10.4% vs 84.7% ± 12.1%, P = 0.04), however cell viability was decreased in a dose- and time-dependent manner. SP600125 blocked the ethanol-induced changes (at 60 min). Additionally, 4-methylpyrazole prevented the ethanol-induced decreases in the IGF-Ⅰ system, cell viability and p-JNK1/2 activity (at 180 min). CONCLUSION: This study suggests that ethanol- induced p-JNK1/2 activation is associated with the IGF-Ⅰ system and cell viability in hepatocytes. Furthermore, alcohol dehydrogenase is involved in the relationship between ethanol-induced inactivation of p-JNK1/2 and the changes of the IGF-Ⅰ system and cell viability. AIM: To evaluate the effects of ethanol on the insulin-like growth factor-I (IGF-I) system involved in c-Jun N-terminal kinase (JNK1 / 2) and alcohol dehydrogenase (ADH) activity in primary cultured rat hepatocytes. : The cells were pretreated with SP600125 (10 μmol / L) and 4-MP (200 μmol / L), and then treated with ethanol (200 mmol / L). We then measured IGF-I secretion, IGF-I mRNA expression, cell viability and JNK1 / 2 activity by radioimmunoassay, RT-PCR, MTT assay and Western blot, Ethanol induced the activity of phospho (p) -JNK1 / 2, reaching a maximum at 60 min and then decreasing at 180 min. The effects of ethanol on the IGF-I system were increased at 60 min (secretion: 7.11 ± 0.59 ng / mg protein vs 4.91 ± 0.51 ng / mg, mRNA expression: 150.2% ± 10.2% vs 101.5% ± 11.3%, P = 0.045) and then decreased at However, cell viability was decreased in a dose of 180 min (secretion: 3.89 ± 0.25 ng / mg vs 5.4 ± 0.54 ng / mg protein; mRNA expression: 41.5% ± 10.4% vs 84.7% ± 12.1%, P = 0.04) time-dependent manner. SP600125 blocked the ethanol-induced changes (at 60 min). 4-methylpyrazole prevented the ethanol-induced decreases in the IGF-I system, cell viability and p-JNK1 / 2 activity CONCLUSION: This study suggests that ethanol-induced activation of p-JNK1 / 2 with IGF-I system and cell viability in hepatocytes. Furthermore, alcohol dehydrogenase is involved in the relationship between ethanol-induced inactivation of p-JNK1 / 2 and the changes of the IGF-I system and cell viability.