Abstract. To determine the involvement of protein kinase C (PKC) in nitric oxide (NO) synthesis of osteoblast, a combination of proinflammatory cytokines (tumor necrosis factor-, interferon-, bacterial lipopolysaccharide) were added on rat osteoblast-like cells. Results show that these cytokines clearly enhanced the synthesis of NO. The activation of PKC with phorbol ester also resulted in the stimulation of NO synthesis in these cells. These cytokines activated PKC and increased the levels of intracellular Ca2+. In addition, the cytokine-induced synthesis of NO was blocked by PKC inhibitors. Findings suggest the involvement of PKC in the synthesis of NO by rat osteoblasts.