Recent studies indicate that the type 2 cannabinoid receptors (CB 2 R ) have become an attractive target for treating a variety of pathologies, including cancers, neurodegenerative diseases, inflammation, pain, osteoporosis, immunological disorders and drug abuse. In addition, it appears that many of these diseases have up-regulated CB 2 R expression. However, the precise role of CB 2 R in the regulation of diseases remains unclear. The ability to specifically image CB 2 R would contribute to develop reliable CB 2 R -based therapeutic approaches with a better understanding of the mechanism of CB 2 R action in these diseases. We developed a CB 2 R -targeted zwitterionic near-infrared (NIR) fluorescent probe, ZW760-mbc94. When compared with a previously reported CB 2 R probe (NIR760-mbc94) with the same targeting moiety but a charged NIR fluorescent dye, ZW760-mbc94 showed improved binding specificity in vitro and ex vivo. Overall, ZW760-mbc94 appears to have great potential as a CB 2 R -targeted contrast agent.