Streptozotocin‐induced, insulin‐deficient diabetic adult rats were daily administrated either minocycline or a chemically‐modified non‐antimicrobial tetracycline (CMT) by oral gavage for a 3‐week time period; untreated diabetic and non‐diabetic rats served as controls. On day 21, all rats received an intravenous injection of ³H‐proline followed by perfusion fixation with an aldehyde mixture at 20 minutes and 4 hours after isotope injection. The upper and lower mandibles of these rats were dissected and processed for quantitative electron microscopic autoradiography to study ³H‐proline utilization by fibroblasts in the periodontal ligament (PDL) of molars. In the non‐diabetic controls, at 20 min after ³H‐proline injection, radioprecursor was incorporated by the Golgi‐RER system of PDL fibroblasts. At the 4‐h time period, most of the label was present over the collagen fibers around these cells. In contrast, PDL fibroblasts in the untreated diabetic rats showed marked abnormalities ultrastructurally and minimal uptake (20 min) and secretion (4 h) of labeled proline. At both time periods, in both minocycline‐ and CMT‐treated diabetic rats, fibroblasts were structurally more normal and the radioprecursor was localized in the fibroblasts and the PDL matrix in a pattern similar to that seen in the control rats. These results suggest that the diabetes‐induced structural abnormalities and suppression of synthesis and secretion of protein (presumably collagen and its precursor) by PDL fibroblasts can be restored to near‐normal by administration of a tetracycline and that this effect is mediated by a non‐antimicrobial property of this family of antibiotics.