Introduction: Reports show that Tetracyclines, especially Minocycline, in addition to anti-microbial effects, have other properties, including anti-inflammatory effects, which are important in various laboratory and clinical models. In this research, the molecular effects of Minocycline on the experimental local inflammation caused by the administration of lipopolysaccharide (LPS) or Endotoxin to the footpads of the rats were investigated by analyzing the expression of the MyD88 gene in an in-vivo model. Methods and Materials: 20 healthy rats were randomly divided into 4 groups including 1) control or without any drug administration, 2) LPS 3) treatment with an appropriate dose of Minocycline alone and 4) Minocycline and LPS treatment. After investigating the inflammation of the rats’ footpad, tissue samples from the inflamed site were taken for real-time PCR assays in order to measure the expression level of MyD88 gene. For this purpose, after extracting the RNA from the rats’ footpad and checking the quality and quantity of RNAs with nanodrop and agarose gel Electrophoresis and cDNA synthesis with special kits. Then samples were tested for comparative investigation of MyD88 gene expression according to specific protocols by qPCR method. Results: During this experiment, the expression level of MyD88 gene was decreased in the group of rats that were administered by Minocycline compared to the group that was injected only with LPS. Conclusion: Minocycline reduces inflammation caused by Endotoxin and bacteria, especially through the reduction of MyD88 gene expression. Further profound research in this area is underway in our laboratory.