BACKGROUND: Astrocytes are considered to provide nutritional support in the central nervous system. However, recent studies have confirmed that astrocytes also play an important role in chronic pain. OBJECTIVE: To investigate the effects of intrathecal injection of fluorocitrate, minocycline or both on astrocyte activation and proliferation in the spinal dorsal horn of compressed dorsal root ganglion in rats. DESIGN, TIME AND SETTING: The neurology randomized controlled animal study was performed at the Jiangsu Institute of Anesthesia Medicine, from September 2006 to April 2007. MATERIALS: A total of 96 male Sprague Dawley rats, aged 6-8 weeks, were selected for this study. Following intrathecal catheterization, 80 rats underwent steel bar insertion into the L4-5 intervertebral foramina to make a stable compression on the L4-5 posterior root ganglion. Thus rat models of ganglion compression were established. Minocycline and fluorocitrate were purchased from Sigma, USA. METHODS: A total of 96 rats were randomly and equally divided into six groups. Rat L4, L5 transverse process and intervertebral foramina were exposed in the sham operation group, but without steel bar insertion. The model group did not receive any manipulations. Rats in the phosphate buffered saline (PBS) group were intrathecally injected with 0.01 mmol/L PBS (20 μL). Rats in the fluorocitrate group were subjected to 1 μmol/L fluorocitrate (20 μL). Rats in the minocycline group were intrathecally injected with 5 g/L minocycline (20 μL). Rats in the minocycline and fluorocitrate group received a mixture (20 μL) of 5 g/L minocycline and 1 μmol/L fluorocitrate. Following model establishment, drugs were administered once a day. MAIN OUTCOME MEASURES: At 7 and 14 days following model induction, glial fibrillary acidic protein expression in the spinal dorsal horn was measured by immunofluorescence microscopy. Six sections with significant glial fibrillary acidic protein -positive expression were obtained to count astrocytes under an inverted microscope. RESULTS: No significant differences in astrocyte count were detected between the fluorocitrate and model groups. Cell bodies were small with a few processes in the fluorocitrate group, compared with the model group. The astrocyte count decreased significantly in the minocycline group and the minocycline and fluorocitrate group compared with the sham operation, model, PBS and fluorocitrate groups (P < 0.01). The decrease in astrocyte count was mainly found in layers Ⅲ-Ⅳ of the spinal dorsal horn. Cell body volume was smaller and process numbers were fewer in the minocycline group and the minocycline and fluorocitrate group, compared with the model and PBS groups. CONCLUSION: Fluorocitrate can inhibit astrocyte activation, but does not affect astrocyte proliferation. However, minocycline can inhibit the activation and proliferation of astrocytes.