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A cholesterol-enriched diet has been shown to adversely affect lipoprotein profiles and increase cardiovascular disease risk. Dietary cholesterol plays an important role in modulating inflammatory responses involved in atherosclerosis. In the present study, the effect of Oryctes rhinoceros larva oil (ORO), an unsaturated fatty acid-rich animal fat, on serum lipid profile and some proinflammatory markers in mice fed a cholesterol-based diet (CBD) was investigated. Forty male Swiss albino mice were randomly assigned to four groups consisting of control (normal diet) and three experimental groups fed normal diet supplemented with ORO, CBD only and CBD supplemented with ORO, respectively. Serum lipid profile, malondialdehyde, C-reactive protein, interleukin-6 and tumour necrosis factor-alpha levels were evaluated before and after diet treatment. Serum triacyglycerol, total cholesterol and low-density lipoprotein cholesterol levels were significantly reduced (P<0.05) in mice fed a CBD diet supplemented with ORO compared with those fed CBD without ORO. In addition, serum malondialdehyde, C-reactive protein and interleukin-6 levels were significantly lower in mice fed CBD suplemented with ORO compared with those fed CBD only (P<0.05). These results suggest that consumption of ORO improved the serum lipid profile and, in addition, may mitigate the attendant adverse inflammatory processes in atherosclerosis.