The protective effect of improving the microcirculation on the retinal ganglion cells (RGC) and the ultrastructure of the optic nerve after intravenous (i.v.) use of Salviae miltiorrhiza (SMR) was studied in a chronic intraocular hypertension model in 36 rabbits. These rabbits were treated with topical 0.5% timolol, or i.v. SMR or i.v. 0.9% saline for 1, 3, 5 or 8 weeks. The intraocular pressure (IOP) was 19.6 +/- 2 mmHg and the RGC density was 1140 +/- 121.2/mm2 in control rabbits. After one week of intraocular hypertension (IOP between 30 and 40 mmHg), the RGC densities decreased to between 650 and 820/mm2. Following the use of timolol for 1 to 8 weeks, IOP returned to control level and the RGC density increased to 1015 +/- 7/mm2. After treatment with i.v. saline for 8 weeks, the RGC density decreased progressively from 651 +/- 1/mm2 at the beginning of treatment to 83 +/- 3/mm2. The RGC density of those rabbits treated with i.v. SMR for 8 weeks remained virtually unchanged (658 +/- 5/mm2) compared to the RGC density at the beginning of the treatment. Severe ultrastructural damage of optic nerve and collapsed capillaries were found in rabbits treated with saline while these findings were mild in rabbits treated with SMR. During these periods of treatment, the intraocular hypertension did not decrease in rabbits treated with either saline or SMR. From these findings and the fact that SMR improves local microcirculation, it is considered that the compromised microcirculation is one of the mechanisms in the pathogenesis of optic nerve damage in chronic glaucoma.