Sensory transient receptor potential (TRP) ion channels present in DRG nerve termini and skin keratinocytes serve a crucial role in detection of environmental harmful stimuli. Little is known about endogenous molecules that negatively control these TRP activities. Resolvins are anti-inflammatory and pro-resolving lipid molecules naturally generated during inflammatory processes. We asked whether D-series resolvins (RvDs) modulate the sensory TRP channel activation. We examined the effects of 17(S)-RvD1 and 17(R)-RvD1 on sensory TRPs using calcium imaging and whole cell electrophysiology experiments with a HEK cell heterologous expression system, cultured sensory neurons and HaCaT keratinocytes. Changes in agonist-specific acute nociceptive behaviors (licks, flicks and flinches) and TRP-related mechanical and thermal pain behaviors were also checked with or without inflammation. As a result, 17(S)-RvD1 targeted multiple TRP channels while 17(R)-RvD1 specifically acted on TRPV3. 17(S)-RvD1 inhibited TRPA1, TRPV3 and TRPV4 at nanomolar and micromolar levels. Consistent decreases in acute pain indices by local administration of 17(S)-RvD1 were also detected. Peripheral treatment of 17(S)-RvD1 significantly prevented mechanical and thermal hypersensitivity in inflamed tissues. For 17(R)-RvD1, TRPV3-specific in vitro and in vivo responses were suppressed upon its application. The administration of 17(R)-RvD1 reversed thermal hypersensitivity caused by inflammation. A molecular mechanism of such inhibition appears to be a shift in voltage-dependence of TRP channels. In conclusion, RvDs are potent endogenous sensory TRP channel inhibitors. The result implicates that our body has an internal antinociceptive potential with endogenous TRP-regulating lipids. This finding may also help understand pain mechanisms involving TRP interactions with pro-resolving substances.