It is shown that lead alters calcium mediated cellular processes in several biological systems. Calcium enhances the activity of protein kinase C (PKC) which takes part in eliciting cell mitosis. In this study, the effects of lead nitrate on the activity of PKC enzyme were investigated in rat liver. The PKC activity was determined at 12, 24, 48, 72, 120, 168 hours after treatment with a single dose of lead nitrate in male Wistar rats. The results showed that the specific PKC activity of the purified particulate fraction was increased and reached a maximum at 24 hour, and lasted for 48 hours. This augmented activity of PKC was parallel with the increase of the lead level in the purified particulate fraction, although the protein levels of PKC alpha, PKC delta and PKC zeta were unchanged. Moreover, the frequency of mitotic cells also exhibited a significant increase, and like PKC activity, reached its maximum at 24 hour with accompany signs of liver enlargement. The results suggest that the PKC activation may be involved in promoting liver cell proliferation in lead nitrate-treated rats.