ABSTRACT The current study reported the synthesis of ferric oxide nanoparticles (Fe2O3 NPs) using the leaf extract of Amaranthus spinosus Linn and studied their analgesia efficiency in chronic inflammatory pain model in mice. X-RD, TEM results showed that the spherical Fe2O3 NPs having rhombohedral crystalline structure with an average particle size of 10 nm. Additionally, inflammatory pain models were designed through FCA injection on the CD1 mice hind paw with various Fe2O3 NPs doses and analgesic behaviour was monitored. The prepared Fe2O3 NPs showed a dose-dependent analgesic activity with considerable decrease in inflammatory cells, ROS production and pro-inflammatory markers. Additionally, the expression of enzymes responsible for ROS production were decreased. The outcomes of present work revealed the local administration of Fe2O3 NPs caused the substantial analgesia through reduction of pro-inflammatory signalling and inflammatory cellular infiltration along with micro-environmental free radical scavenging in mouse inflammatory pain model.