The aim of this study was to establish the effects of fluoride on lipid metabolism and attendant inflammatory response by exposing rats to 50 mg L-1 and 100 mg L-1 of fluoride through drinking water for seven weeks. Both concentrations led to hypercholesterolemia while the 100 mg L-1 concentration induced hypertriglyceridaemia. High density lipoprotein (HDL) cholesterol levels dropped in the exposed rats while interleukin 2 (IL-2) increased more than 1.5-fold (p<0.05) and IL-6 and plasma TNF-α more than 2.5 fold (p<0.05). Fluoride-exposed rats also had significantly higher levels of liver malondialdehyde (MDA) and plasma lipid hydroperoxide (LOOH) but lower plasma paraoxonase (PON1) activity. Oxidative stress indices correlated with pro-inflammatory cytokines and plasma cholesterol. In contrast, proinflammatory cytokines inversely correlated with plasma triglyceride, HDL cholesterol and PON1. Our results suggest that the association between fluoride exposure with cardiovascular diseases may be related to its ability to disturb lipid homeostasis, and trigger pro-inflammatory cytokines and oxidative stress.