Background: The intestinal absorption of fatty acids may take place through simple diffusion as well as through protein carrier mediated transport, although the relative importance of each pathway is dependent on the ambient condition of entrocytes. Cadmium ion influences the absorption of fatty acids in entrocytes. However, the effect of cadmium ion on the absorption of fatty acids in different pH values has not been evaluated yet. Especially, the luminal pH of small intestine has an essential role in the absorption of fatty acids. In the present study we aimed to evaluate reciprocal effects of cadmium ion and pH of intestine lumen on the absorption of fatty acids in rat model. Methods: In this experimental research, 3 months old Wistar rats (45 rats) were used for experiments. After killing the rats, their intestine was removed and the duodenum and jejunum segments were dissected. Everted Gut Sacs (EGS) were prepared from these duodenum and jejunum segments. The sacs were filled with buffer solution and incubated in a medium containing an appropriate concentration of oleic acid. Then the amounts of oleic acid that had been absorbed into the EGSs in the presence and absence of cadmium ions under different conditions of pH, was measured. Results: Findings of the study demonstrated that the luminal pH of small intestine was effective on the oleic acid uptake and the inhibitory effect of cadmium ions on the uptake of the acid was influenced by pH condition, so that this inhibitory effect was 32 and 36 at the alkaline pHs 7.5 and 9.2, respectively (P< 0.05). At the acidic pHs, 2.5 and 4.5, the inhibitory effect reduced to 11 and 5, respectively (P< 0.05). Conclusion: Cadmium ion decreased fatty acid uptake by small intestine in rats, and the acidic pH of intestine lumen could attenuate the inhibitory effect of cadmium ion