Odors have been shown to exert an influence on various physiological and behavioral activities. However, little is known whether or not odor stimulation directly affects the levels of feeding-related neuropeptides. Here we show that the neural transmission by Osmanthus fragrans (OSM) decreased the mRNA expression of orexigenic neuropeptides, such as agouti-related protein, neuropeptide Y, melanin-concentrating hormone and prepro-orexin, while increased anorexigenic neuropeptides, such as cocaine- and amphetamine-regulated transcript and proopiomelanocortin in rats. The decreased number of orexin-immunoreactive neurons in the hypothalamus coincided well with the OSM-induced decreases in the expression of prepro-orexin mRNA. This study demonstrates that the OSM odor, which is known to have a mild sedative effect, decreases the motivation to eat, food intake and body weight, accompanied by sluggish masticatory movements. The data suggest that these effects are due to suppression of orexigenic neuropeptides and activation of anorexigenic neuropeptides in the hypothalamus.