), time taken to reach C (T ), areas under time-concentration curves (AUC and AUC ), t ), meanresidence time (MRT), clearance (Cl), zero concentration (C ), steady state volume of distribution (V ), and BA. Additionally, for safety evaluation, animals were treated orally with aqueous solution of acyclovir, drug-free semisolid SMEDDS and acyclovir-loaded semisolid SMEDDS, during 21 days (groups 4–7). Serum samples of sacrificed animals were used for biochemical analysis of enzymatic activity of alanine transaminase (ALT) and aspartate transaminase (AST), urea, creatinine, and uric acid. Acyclovir administered by semisolid SMEDDS reached twice higher C (0.92 ± 0.21 μg/ml) and has significantly shorter T (14 ± 10.84 min) compared to the suspension of acyclovir (C 0.29 ± 0.09 μg/ml and T 26.00 ± 5.48 min). BA of the drug was significantly increased by semisolid SMEDDS, while the analysis of biochemical parameters excluded damage on function of liver and kidneys caused by the investigated drug delivery system.