Secretory phospholipase A2 group IIA (PLA2G2A) is a member of a family of secretory phospholipases which have been implicated in inflammation, atherogenesis and antibacterial actions. Here, we evaluated the role of PLA2G2A in the metabolic response to a high fat diet. C57BL/6 mice do not express PLA2g2a due to a frameshift mutation. We fed C57BL/6 mice expressing the human PLA2G2A gene (IIA+ mice) a fat diet and assessed the physiologic response. After 10 weeks on the high fat diet, the C57BL/6 mice were obese, but the IIA+ mice did not gain weight or accumulate lipid. The lean mass in chow and high fat fed IIA+ mice was constant and similar to the C57BL/6 mice on a chow diet. Surprisingly, the IIA+ mice had an elevated metabolic rate which was not due to differences in physical activity. The IIA+ mice were more insulin sensitive and glucose tolerant than the C57BL/6 mice even when the IIA+ mice were provided the high fat diet. The IIA+ mice had increased expression of uncoupling protein 1 (UCP1), Sirtuin 1 (SIRT1) and perosixome proliferator-activated receptor gamma coactivator (PGC-1alpha) in brown adipose tissue, suggesting that PLA2G2A activates mitochondrial uncoupling in brown adipose tissue. Our data indicate that PLA2G2A has a previously undiscovered impact on insulin sensitivity and metabolism.