Lipid microspheres (LMs) have recently been use as drug carriers for intravenous use due to its low toxicity, good physiological tolerance and the reduction of the drug related side-effect. In this study, clarithromycin was incorporated in LMs, in an attempt to reduce the pain caused by intravenous use. The composition of the drug loaded LMs was clarithromycin 0.5%, oil phase 10%, soybean phospholipid 2%, egg lecithin 0.5%, Sodium oleate 0.1%. Clarithromycin LMs was prepared by high pressure homogenization method at 80 MPa for 8-10 cycles. The mean particle size and surface charge of LMs were $208.7{pm}7.8nm;and;-23.6{pm}2.3mv$ respectively. Clarithromycin entrapment efficiency in LMs was 66.4%. Drug loaded LMs was stable during the storage time at $6{pm}2^{circ}C$ for 9 month, and the particle size and zeta-potential did not change significantly. Drug concentration in LMs was 5 mg/mL, and there was no drug degradation during long term storage. Animal tests (rat paw lick test and rabbit ear vein irritation test) were used to evaluate the pain reduction of clarithromycin LMs compared with that of clarithromycin aqueous solution. These results suggest that the LM system is a promising option to replace clarithromycin aqueous solutions as an intravenous treatment.