The influence of adjuvants in suppository formulations on the release and absorption of sodium valproate, a water soluble anti-epileptic, was analysed in order to determine the optimal formula for rectal administration. Three formulations were prepared with Suppocire AS2(formula I), Aerosil R 972 (formula II) or Span 80 (formula III). In-vivo and in-vitro release-diffusion studies were performed using white laboratory rabbits as the experimental model. The adjuvants decreased the percentage release of valproic acid to 96.7% (formula I) and 84.1% (formula II), and delayed peak release-diffusion concentration (210 and 150 min, respectively, with formulas II and III in comparison with 120 min with formula I). Their effect on bioavailability was observed as an increase in plasma levels of the active substance, with areas under the plasma concentration/time curve of 396.26 and 306.64 micrograms h mL-1 (formulas II and III, respectively) and 243.28 micrograms h mL-1 (formula I). The time to peak plasma concentration was also delayed with peaks at 30, 55 and 50 min with formulas I, II and III, respectively.