Objective To observe the long-term impact of dietary fatty acids on fatty acids composition and relative gene exp ression of brain in the offsp ring of C57BL /6J mice fed with high fat high energy diet. Method Eight-week-old healthy C57BL /6J mice, after adap tion for one week, were caged with a ratio of 2∶1 for female and male. Matingwas confirmed in the nextmorning by the p resence of vaginal p lug. Twenty four dams were housed individually and divided into three group s fed with normal chow diet, linoleum oil diet or lard diet respectively. The offsp ringwere fed with the same dietwith theirmother from ablactating until 9 weeks old. Fatty acids of brain were analyzed by gas chromatography and exp ressed as percent (% ) of total fatty acids. The relative exp ression ofβ-actin, lxra, acc, fas and scd-1 genes were analyzed by RT- PCR. Results The composition of SFA ( saturated fatty acid ) were significantly increased, whereas PUFA (polyunsaturated fatty acid) , especially DHA ( docosahexaenoic acid) , was significantly decreased in the offsp ring of lard diet group compared with that of normal chow diet group. The exp ression of lx ra, acc and scd-1 were up-regulated in the offsp ring of linoleum oil diet group, and the exp ression of fas was up-regulated in lard diet group. Conclusion The brain fatty acid composition of the offsp ring from the dam fed with high fat high energy diet might be affected by regulating the exp ression of relative gene of fatty acid synthesis.