Arsenic is a widespread environmental toxicant in the world and regarded as both a carcinogen and an anticarcinogen. The present study was designed to evaluate roles of mitogen-activated protein kinases in sodium arsenite-induced effects on primary-cultured rat cerebellar granule neurons (CGNs). Results revealed a decreased viability of the cells exposed to sodium arsenite (from 0 to 50 μM) in a dose-dependent manner. Annexin V-fluorescein isothiocyanate assay showed that apoptosis was obviously induced by arsenite treatment. High phosphorylation expressions of p38 and extracellular signal-regulated kinases (ERK1/2), but not of c-Jun N-terminal kinases were observed due to arsenite treatment by western blotting analysis. Furthermore, SB203580 (an inhibitor of p38) decreased the percentage of apoptotic cells whereas arsenite-stimulated toxicity was enhanced by U0126 (an inhibitor of ERK1/2). Taken together, these data suggest that p38 contributes to arsenite-induced apoptosis of rat CGNs, but ERK1/2 may involve in cell growth and survival.