The purpose of this study was to evaluate the effect of sodium carboxymethylcellulose (NaCMC) and carboxymethylcellulose-cysteine (CMC-Cys) conjugates on the intestinal permeation of sodium fluorescein (NaFlu) and model peptide drugs, bacitracin and insulin. Cysteine was covalently linked to carbodiimide activated NaCMC. Iodometric titration of the polymer conjugates was used to determine the extent of immobilised cysteine. Permeation studies were performed on guinea pig small intestinal mucosa mounted in Ussing-type chamber. Unmodified NaCMC (1% m/v) significantly improved the transport ratio (R= P(app) polymer/ P(app) control) of NaFlu to 1.3 and 1% (m/v) NaCMC conjugated with cysteine further enhanced the permeation. Cysteine conjugation at 3.6, 5.3 and 7.3% (m/m) resulted in R-values of 1.4, 1.7 and 1.8, respectively. Decreasing the concentration of CMC-Cys, exhibiting 7.3% (m/m) of immobilised cysteine (CMC-Cys7.3) from 1% (m/v) to 0.5% (m/v) decreased the R-value of NaFlu from 1.8 to 1.2. NaCMC at 1% (m/v) in the presence of free cysteine had no significant effect on the R-value of NaFlu compared to NaCMC alone. Formulation of fluorescence labelled bacitracin and insulin in unconjugated NaCMC (1% m/v) did not significantly improve the permeation, however in the presence of 1% (m/v) CMC-Cys7.3 a significantly improved permeation was observed (R= 1.3). Conjugation at NaCMC with cysteine moieties significantly improves the intestinal permeation of the hydrophilic molecule NaFlu and the model peptide drugs bacitracin and insulin in vitro, therefore this conjugated system maybe useful for peroral administration of peptide drugs in the future.