Effects of sesamin and curcumin on delta 5-desaturation and chain elongation of polyunsaturated fatty acid (PUFA) were studied in rat primary cultured hepatocytes. When sesamin was added to culture medium containing 20:4 (n-3), rat hepatocytes after 24 h of incubation produced 20:5 (n-3) from 20:4 (n-3), whereas when incubated with 20:3 (n-6), the metabolite by delta 5-desaturation did not accumulate, and consequently, the ratio of 20:3 (n-6)/20:4 (n-6) increased with the amount of sesamin added. Curcumin was more effective than sesamin in this respect. Both sesamin and curcumin interfered with chain elongation of PUFAs. An addition of 18:3 (n-6) or 18:4 (n-3) increased the cellular concentrations of 20:3 (n-6) or 20:4 (n-3), respectively, but the simultaneous addition of sesamin or curcumin inhibited the chain elongation of C18 acids (the fatty acids with 18 carbons) into corresponding C20 and C18 acids. Similarly, the elongation from C20 of n-3 and n-6 families to C22 was also inhibited with sesamin and curcumin. These results suggested that: 1) sesamin and curcumin inhibited delta 5-desaturation of n-6 fatty acid, but not n-3 fatty acid in rat hepatocytes; 2) curcumin was more effective than sesamin; 3) chain elongation was also inhibited by sesamin and curcumin.