Abstract: Nitrite, a common pollutant in aquaculture, is an intermediate product of nitrogen cycle in ecosystem. To explore the mechanisms of sodium nitrite-induced cell apoptosis, grass carp liver cell (L8824) were exposed to four concentrations of sodium nitrite (0, 5 mg/L, 20 mg/L and 50 mg/L) with or without treatments of phosphoinositide receptor antagonist 2-APB and IRE1 inhibitors STF-083010. Cell apoptosis related gene expression of jnk, bcl-2, bax, caspase9, caspase3, ire1α, xbp1s and grp78 and the cytoplasmic calcium ion concentration were assessed. The results showed that nitrite significantly increased the apoptosis rate, cytoplasm calcium ion concentration and mRNA levels of jnk, bax, caspase9, caspase3, ire1α, xbp1s and grp78 and significantly decreased bcl-2 mRNA level, which were reversed by the STF-083010 treatment. Besides, both 2-APB and STF-083010 reduced the sodium nitrite-induced cytoplasmic calcium ion. These results indicate that endoplasmic reticulum stress-related IRE1 pathway plays pivotal role nitrite-mediated L8824 cell apoptosis and calcium dyshomeostasis.