Amikacin-, vancomycin- or amikacin/clindamycin-impregnated gel was placed subcutaneously on either side of horses' necks a total of 6 times each. Interstitial fluid was collected at 0, 4, 8, 12 and 24 hours, and days 2 through 10, via capillary ultrafiltration probes placed within the incision (0cm) and 1.5cm laterally. Plasma or serum was collected at days 0, 1 and 7. Biopsy samples were obtained at the completion of the study. A histomorphologic score was assigned to each sample, and the differences in mean scores between treatment (gel) and control incisions were assessed using Wilcoxon signed rank test. Amikacin and vancomycin samples were analyzed via fluorescence polarization immunoassay; clindamycin samples were analyzed via high performance liquid chromatography. Concentrations greater than 2000 times the MIC of vancomycin and clindamycin, greater than 1000 times the MIC of amikacin, and greater than 800 times the MIC of amikacin (amikacin/clindamycin gel) were obtained at 0cm. Mean concentrations remained above MIC for vancomycin and clindamycin for 10 days (0cm) and 8 days (1.5cm); for 9 days (0cm) and 7 days (1.5cm) for amikacin gel; and for 9 days (0cm) and 5 days (1.5cm) for amikacin (amikacin/clindamycin gel). Mean plasma amikacin and vancomycin concentrations were negligible; serum clindamycin concentrations were greater than MIC (0.52µg/ml and 0.63µg/ml) at 24 hours and 7 days respectively. There were no significant differences in histomorphologic scores between treatment and control incisions. Cross-linked dextran gel is a safe, effective alternative for local antibiotic delivery in horses, with substantially high local concentrations and minimal systemic absorption for amikacin- and vancomycin-impregnated gels.