This study was designed to determine whether lipocalin type-prostaglandin D synthase (l-pgds) deficiency contributes to atherogenesis using gene knockout (KO) mice. A high-fat diet was given to 8-week-old C57BL/6 (wild type; WT), l-pgds KO (LKO), apolipoprotein E (apo E) KO (AKO) and l-pgds/apo E double KO (DKO) mice. The l-pgds deficient mice showed significantly increased body weight, which was accompanied by increased size of subcutaneous and visceral fat tissues. Fat deposition in the aortic wall induced by the high-fat diet was significantly increased in LKO mice compared with WT mice, although there was no significant difference between AKO and DKO mice. In LKO mice, atherosclerotic plaque in the aortic root was also increased and, furthermore, macrophage cellularity and the expression of pro-inflammatory cytokines such as interleukin-1beta and monocyte chemoattractant protein-1 were significant increased. In conclusion, l-pgds deficiency induces obesity and facilitates atherosclerosis, probably through the regulation of inflammatory responses.