The effect of aqueous extract of the leaves of Chromolaena odorata on body weight, organ sizes, lipid profiles and atherogenic indices was investigated in normal and sub-chronic salt-loaded rats. The normal and treatment control groups were fed 100% of commercial feed, while the test control, reference and test treatment groups received an 8% salt-loaded diet. The extract (at 100 and 200 mg/kg body weight) and moduretics (at 1 mg/kg body weight) were orally administered daily. The normal and test control groups orally received appropriate volumes of water. The extract was screened for bioactive components using gas chromatography-coupled-flame ionization detector. The main glycosides, saponins, allicins, alkaloids, benzoic acid derivatives, terpenes and lignans detected were arbutin, avenacin B-1 (and avenacin A-1), diallyl thiosulphinate, lupanine, ferulic acid (and vanillic acid), limonene and retusin, respectively. Compared to test control, the extract dose-dependently, significantly (P < 0.05) lowered the heart size, plasma levels of triglyceride, total density lipoprotein, very low density lipoprotein, low density lipoprotein and non-high density lipoprotein cholesterol and atherogenic indices (cardiac risk ratio, atherogenic coefficient and atherogenic index of plasma). It also significantly increased plasma high density lipoprotein level. These results suggest a protective mechanism of the extract against hypertension induced cardiomegaly and dyslipidemia, thus suggesting that this may underlie its antihypertensive action.