Objective: Investigate the effect of ethanol, polyethylene glycol 400, propylene glycol, glycerol and sorbitol on the absorptive clearance of ketotifen fumarate   in the rabbit. Methods: In-situ intestinal perfusion technique, ̎through and through ̎ was used for estimation of membrane transport parameters of ketotifen fumarate from duodenum, jejunum, ileum and ascending colon in the rabbit. These parameters include absorptive clearance per unit length PeA/L (ml/min.cm), percentage fraction absorbed per unit length (% Fa/cm) and anatomical length that required for complete absorption in specific segment (L95%). Results: The absorption was in the order ascending colon> duodenum > jejunum> ileum; where the absorptive clearance normalized to intestinal segment length PeA/L (ml/min.cm) was 0.0071 ± 0.0003, 0.0058 ± 0.0001, 0.0051 ± 0.0001, and 0.0047 ± 0.0001 in each segment respectively. The effect of cosolvents in jejunum was in the order; ethanol 15% >glycerol 30% > propylene glycol (PG40%) > polyethylene glycol400 (PEG-400 40%) >sorbitol 40%, Where the absorptive clearance normalized to intestinal segment length PeA/L (ml/min.cm), mean ± SE was: 0.0142 ±0.0011, 0.0086 ± 0.0002, 0.0075 ± 0.0003, 0.0022 ± 0.0001, and 0.0014 ± 0.0001 for each cosolvents respectively. The same order was obtained in the ascending colon. Conclusion: The enhancing action of the ethanol, propylene glycol and glycerol may be due fluidization of the cell membrane with a subsequent increase in transcellular absorption, while the inhibitory effect of polyethylene glycol and sorbitol could attributed to water secretion, H-bonding formation and reduced thermodynamic activity of drug molecules.