The solubilities of penicillin sulfoxide in ethyl acetate, 4-methyl-2-pentanone, butyl acetate, and toluene from (273.15 to 332.75) K were measured with the mole fraction by a gravimetric method The Solubilities in these solvents are temperature dependent. The results show that the Solubility of penicillin sulfoxide in toluene is very low, so toluene is considered as one of the best solvents and used in industry. According to the results, we can see that the Solubilities of penicillin sulfoxide in ethyl acetate, 4-methyl-2-pentanone, butyl acetate, and toluene can be correlated well with a semiempirical equation.