During perinatal development, the regulation of IGF system appears to be GH independent. By using highly purified primary foetal hepatocytes, we investigated the role of prolactin in the regulation of IGF system and hepatocytes proliferation. We also analyzed the consequence of maternal low protein (LP) diet on the regulation of IGF, IGFBP and hepatocytes proliferation by prolactin. Pregnant Wistar rats were fed a control (C) diet (20% protein) or isocaloric (LP) (8%) diet throughout gestation. At day 21.5, foetal hepatocytes were cultured during four days and incubated with rat prolactin. In the C hepatocytes, PRL at 100 ng/ml decreased the abundance of IGFBP-1 and IGFBP-2 by respectively 50% (P<0.05) and 60% (p<0.01). It reduced also by 70% the level of IGF-II mRNA (p<0.01). By contrast, PRL failed to modulate IGFBP-1 and IGFBP-2 production by LP hepatocytes and this was associated with reduced abundance of the short form of prolactin receptor (p<0.05). PRL had no effect either on the proliferation or the IGF-I production by C and LP hepatocytes while it reduced the expression of IGF-II. These results suggest that prolactin influences hepatocytes proliferation in vitro both by inhibiting IGFBP-1 and IGFBP-2 and IGF-II levels, which may coincide with the decline of IGF-II, observed in rodents during late gestation in vivo. On the other hand, maternal LP diet induces a resistance of foetal hepatocytes to prolactin.