A new platform for oral delivery of paclitaxel (PTX) was developed through chemical conjugation of PTX to a low molecular weight chitosan (LMWC). The LMWC-PTX conjugate contained approximately 12 wt % PTX and showed greatly enhanced water solubility (>1 mg/mL) as compared to native PTX. The conjugate showed comparable IC 50 values to that of the parent PTX against human cancer cell lines. The pharmacokinetic data revealed approximately 42% of bioavailability after oral administration of 5 mg PTX/kg of the conjugate. When the conjugate (10 mg/kg based on PTX content) was administered orally to mice bearing xenograft or allograft tumors, the conjugate-treated group showed significant inhibition of tumor growth, which was comparable to that seen with PTX of the clinically available injected form, formulated in cremophor EL/ethanol (iv) but with much lower toxicity. Tracking I (125)-labeled conjugate showed that LMWC-PTX was likely to be absorbed mainly from the ileum and reach the blood as the intact conjugate.