Introduction: Propolis has been known for its antibacterial properties in medicine and cosmetics. The consumption of raw propolis restricts these benefits due to low bioavailability, low solubility and low absorption. Different nanoencapsulation technologies are used to increase water solubility and antibacterial properties of Propolis extract. The aim of this study is to synthetize solid lipid nanoparticles (SLNs) of khorasani Propolis ethanol extract (EEP) and determine its antibacterial activity against Escherichia coli, Staphylococcus aureus, Bacillus subtilis and Pseudomonas aeruginosa. Materials and Methods: The mixture, ultrasonic for 2 min (20 w at 25°c) and then immediately, 15 ml cold water added to the mixture to form SLN. The synthesized SLN size determined by dynamic light scattering (DLS). The minimum inhibitory concentration (MIC) of synthetized Propolis ethanol extract SLN (PEESLN) against four pathogenic bacteria was evaluated by broth microdilution method in a range of 0.5-4 mg/ml. The MBC was determined by the lowest concentration that kills 99.9% of the initial bacterial population. Results: DLS result showed that PEESLN has less than 100 nm particle size. The MIC value of PEESLN against E. coli, S. aureus, B. subtilis and P. aeruginosa, was calculated 1,1,0.5 and 4 mg/ml, respectively. The MBC value of EEP was same as MIC except for E. coli (2mg/ml). Th e results exhibited that, PEESLN had better inhibitory effect on Gram positive bacteria than Gram negative bacteria. Conclusion: synthetized PEESLN showed good water stability and antimicrobial activity. It could be considered as an antimicrobial agent in several materials such as wound band, toothpaste and etc.

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