The importance of drug lipophilicity on absorption from the liver surface was examined in rats using paraben derivatives, antipyrine, Sudan III, and Sudan blue. The log partition coefficient (PC) of n-octanol/water ranged from -1.39 to 4.62. The compounds were applied to the rat liver surface using a cylindrical diffusion cell (i.d. 9 mm). The rate of absorption at 15 min was calculated to be 13.9% for paraben, much lower than that for its derivatives methylparaben, propylparaben and butylparaben (∼ 80%). The obtained first-order absorption rate constant (k(a) ) of paraben, methylparaben, propylparaben and antipyrine increased according to lipophilicity. Further lipophilicity resulted in a fall in k(a) , implying the importance of affinity for lipids and water in absorption from the liver surface. Thus, a compound with a log PC of around 2.5 is considered to have maximum absorbability from the rat liver surface. A good relationship (r(2) = 0.97) was recognized between the log k(a) and log reciprocal value with the square root of molecular weight of the compounds with a log PC below 2.5. The rate of absorption of a drug from the liver surface could be estimated from physicochemical properties such as lipophilicity and molecular weight. © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.