AbstractRats implanted with multiperforated subcutaneous plastic capsules were used as a model for study of the penetration of four cephalosporins into sites infected withEscherichia coli.The concentrations of the antibiotics were determined in uninfected and infected cages microbiologically up to 4 h after treatment. All four cephalosporins entered infected capsules faster than the control ones and the peak concentrations were attained 30–60 min earlier. The clearance of the antibiotics from infected capsules was faster than from uninfected ones, probably due to inactivation by microbial β‐lactamase(s). Serum protein binding may account for differences in the penetration rate of cephalosporins, but serum level and serum half‐time seem to contribute to their kinetic profile in tissue