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Retinoic acid (RA) has been considered a pro‐apoptotic agent, and little is known about its anti‐apoptotic potential. In this article, we describe that RA strongly inhibits hydrogen peroxide (H₂O₂)‐induced apoptosis of mesangial cells by intervention in activator protein 1 (AP‐1). Our data showed that: (i) H₂O₂ induces apoptosis of mesangial cells via the AP‐1 pathway; (iii) activation of AP‐1 by H₂O₂ is mediated by the c‐Jun N‐terminal kinase (JNK)–c‐Jun/AP‐1 pathway and the extracellular signal‐regulated kinase–c‐Fos/AP‐1 pathway; (iii) RA inhibits H₂O₂‐induced apoptosis via suppression of c‐fos/c‐jun expression and JNK activation; and (iv) the anti‐apoptotic effect of RA is, at least in part, mediated by induction of mitogen‐activated protein kinase phosphatase 1.