The aim of this study is to investigate the antioxidant and intracellular anti-inflammatory efficacy of blueberry leaf extracted with hot water (BLW), 70% ethanol (BLE), and 70% acetone (BLA) in RAW 264.7 macrophages. In order to evaluate the anti-inflammatory effect of blueberry leaf extracts, RAW 264.7 macrophages were stimulated with lipopolysaccharide (LPS) to induce the production of inflammation-related factors, which were measure by Western blotting and real-time PCR methods. i-NOS, COX-2 protein, and mRNA expression showed concentration-dependent decrease. The decreases in the mRNA expression levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) were concentration-dependent. Further, the antioxidant effects of blueberry leaf on total polyphenol contents, electron donating ability and ABTS+ radical scavenging activity were evaluated. The total polyphenol contents of BLW, BLE, and BLA were 217.04±2.98, 156.72±3.90, and 182.88±3.02 mg TAE/g, respectively, while the electron donating abilities at 1,000 μg/mL of BLW, BLE, and BLA were 81.7, 79.6, and 79.3%, respectively. The ABTS+ radical scavenging activity was fond to be concentration dependent. The nitric oxide (NO) production inhibition activities at 50 μg/mL of BLW, BLE, and BLA were 35.1, 42.4 and 42.7%, respectively. In conclusion, the antioxidant and anti-inflammatory test results indicate that blueberry leaf extracts (BLW, BLE, and BLA) can be used as potential anti-inflammatory agents.