The purpose of this paper is to prepare a less-irritating and lipid-based clarithromycin complex (LCC) by the route of intravenous administration qualified with high drug-loading and fine particle size. The LCC was prepared by the injection of organic solvent phase (containing clarithromycin, sodium cholesterol sulfate and phospholipid at a molar ratio of 1:1:1.5) into the Tris buffer solution (0.05 M, pH 7.2) at 40 °C, and then was concentrated by ultrafiltration to remove the organic solvent. The technique of lyophilization was applied to obtain the LCC lyophilized products. Evaluation of the injectable LCC was performed by particle sizes analysis, transmission electron microscope, entrapment efficiency, stability and irritation tests. The LCC possessed a log-normal size distribution with an average size of 75.4 nm. The drug entrapment efficiency was above 97.0%, which was influenced by the amount of phospholipid, pH value of the media and ionic strength of aqueous suspension. The results of stability and irritation tests proved that LCC had more stability and less irritation. This unique LCC formulation may be applied to the human by the route of injection with less or no irritation. LCC could be an appropriate candidate for intravenous preparation and has a great potential for clinical and industrial-scale production.