Summary: Primary rat hepatocytes were cultured using different in vitro models and the enzymeleakage, albumin secretion, and cytochrome P450 lA (CYP lA) activity were observed. The re-sults showed that the level of LDH was decreased over time in culture. However, on day 5, LDHshowed a significant increase in monolayer culture (MC) while after day 8 no LDH was detectablein sandwich culture (SC). The levels of AST and ALT did not change significantly over the inves-tigated time. The CYP lA activity was gradually decreased in a time-dependent manner in MC andSC. The decline of CYP lA was faster in MC than in SC. This effect was partially reversed by us-ing cytochrome P450 (CYP450) inducer such as Omeprazol and 3-methylcholanthrene (3-MC) andthe CYP 1A induction was always higher in MC than in SC. In bioreactor basic CYP lA activitywas preserved over 2 weeks and the highest albumin production was observed in bioreactor fol-lowed by SC and MC. Taken together, it was indicated each investigated model had its advantagesand disadvantages. It was also underlined that various in vitro models may address different ques-tions.