Cells undergo apoptosis when they are subjected to prolonged ER stress (ERS). Excessive lipid deposition causes ERS in adipocytes; however, it rarely serves as a stress factor that triggers apoptosis. This strongly implies that an anti-ERS mechanism may exist in differentiating adipocytes. We used 3T3L1 (adipocytes) and C2C12 (myocytes) to probe for a potential anti-ERS mechanism. After cells were induced to adipogenesis or myogenesis, they were treated with the ERS inducer, tunicamycin. After tunicamycin-mediated ERS, the expression of the key molecular chaperone, Bip, increased in both cell lines. The chaperone, GRP94, responded differently to extended tunicamycin treatment, with protein levels remaining largely unchanged in 3T3L1 cells but falling in C2C12 cells. In terms of CHOP expression, C2C12 cells contained higher levels than 3T3-L1 cells. When GRP94 expression was reduced by siRNAs, CHOP expression increased. Considering the high levels of GRP94 in 3T3L1 cells under ERS, the small rate of apoptosis in 3T3L1 cells might result from the downregulation of CHOP mediated by GRP94. When C2C12 cells were pretreated with taurine, GRP94 levels appeared to increase and CHOP expression decreased. These results strongly imply that taurine may play an important role in promoting GRP94 expression and blocking the progression to apoptosis under ERS through the inhibition of CHOP upregulation.