The steady-state flux of 33 substituted quinoline derivatives was determined in polydimethylsiloxane membranes using isopropyl alcohol as the receiver solvent. These diffusants constituted a diverse group of compounds possessing a wide range of hydrophobic, steric, and electronic characteristics. Various parameters representing these physicochemical properties such as cyclohexane–water fragmental constants, molar refractivity, Hammett's σ constants, intramolecular hydrogen bonding ability, melting point, and mole fraction solubility were employed to develop empirical models capable of relating the rate of diffusion to these characteristics of either the substituent on the quinoline ring or the compound itself.