We previously found that intracerebroventricular injections of resolvin E1 (RvE1) and E2 (RvE2) produce antidepressant-like effects in lipopolysaccharide (LPS)-induced depression model mice. However, these compounds or analogs should be administered noninvasively for clinical use. We recently found that treatment with RvE1 via intranasal (i.n.) route produces antidepressant-like effects in LPS-challenged mice. The antidepressant-like effects of i.n. RvE1 require brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor release and the subsequent mechanistic target of rapamycin complex 1 (mTORC1) activation in the medial prefrontal cortex (mPFC). Intranasal RvE1 also produces antidepressant-like effect via intra-mPFC mTORC1 activation in repeated prednisolone-induced depression model mice. We also found that intraperitoneal injection of a metabolically stable RvE2 analog o-BZ-RvE2, but not RvE2, produces antidepressant-like effects in LPS-challenged mice. Moreover, oral (p.o) administration of o-BZ-RvE2 produces antidepressant-like effects in LPS-induced depression model and ovariectomized mice that display depression-like behavior, and the effects require BDNF release and mTORC1 activation in the mPFC. Thus, RvE1 and o-BZ-RvE2 can be promising leads for the treatment of depression.