The present study aimed to evaluate the lethality, residues and toxicokinetics of acetone in serum of male albino rats as a mammalian model, throughout forty-eight hours following a single intubation. The lethality percentile doses (LD_S): LD₁ to LD₉₉ of acetone at 24 hours were estimated, after oral-intubation of acetone. The computed LD₅, LD₃₀ and LD₅₀ were 1.3, 3.0 and 4.6 g/kg body weight, respectively. Three groups of male albino rats were orally-intubated with a single dose of 0 g (group 1: control), LD₅ (group 2) and LD₃₀ (group 3) of acetone/kg body weight. The residues of acetone in serum of group 1, 2 and 3, and the areas under curves (AUC and AUC_cum) and areas under moment curves (AUMC and AUMC_cum) in serum of group 2 and 3, were significantly affected by the experimental periods (1, 6, 12, 24 and 48 hours), intubated doses (0, 1.3 and 3.0 g) and their interactions. The acetone residues of group 2 and 3 showed negative exponential relationship with the experimental periods, with correlation coefficients (r) -0.95 and -0.72 respectively, whereas the AUC, AUC_cum, AUMC and AUMC_cum showed positive correlation coefficients (r) +0.64, +0.91, +0.96, +0.98, +0.99, +0.99, +0.99 and +0.99, respectively. The residues of acetone in rats of group 3 were significantly > the group 2> group 1 (control). In comparison with rats of group 2, the AUC_total, AUMC_total, half-life of elimination (t_1/2); the mean retention time (MRT) of acetone in serum of group 3, were significantly increased, whereas the total clearance (CL) and the elimination rate constant (L_Z) were markedly decreased, at all the experimental periods. In conclusion, the toxicokinetics of acetone in serum of mammals were time- and dose-dependent.