Intra-articular lipopolysaccharide is a common model to induce acute synovitis to investigate the effects of various therapeutic agents or nutraceuticals. The long-term effects of intra-articular lipopolysaccharide use in skeletally mature and immature horses has yet to be investigated; therefore, the objective of this study was to describe long-term effects of single-administration of intra-articular lipopolysaccharide on joint inflammation and cartilage metabolism. To test this objective, both radial carpal joints from 5 stock-type horses never exposed to lipopolysaccharide (CON; n = 10) were compared to radial carpal joints from 17 similar stock-type horses previously exposed to intra-articular lipopolysaccharide (INFL; n = 34). Joints within INFL were further categorized as the joint which received lipopolysaccharide (LPS; n = 17) and contralateral control which received iso-volumetric lactated Ringer’s solution (CONTRA; n = 17). A single synovial fluid sample from each joint was analyzed for prostaglandin E2 (PGE2), collagenase cleavage neopeptide (C2C), carboxypeptide of type II collagen (CPII), and chondroitin sulfate 846 (CS846). All data were analyzed using PROC MIXED of SAS with main effects of treatment (CON, INFL) and joint (CON, LPS, CONTRA). Time post-administration (1.5, 2, 6 yr) and age-at-administration (1, 3, 5, 7 yr) were included in the model within INFL joints (LPS, CONTRA). There was no influence of treatment on any biomarker (P < 0.40). Similarly, inflammation and cartilage metabolism were not different between CON, CONTRA, and LPS joints (P < 0.50). Within INFL, there was no influence of joint, age, or time post-administration for PGE2, CPII, or CS846 (P < 0.10). A joint x time interaction was observed for catabolic C2C (P > 0.01); however, where LPS was less than CONTRA 2 yr post-lipopolysaccharide administration and similarly when lipopolysaccharide was administered at 5 and 7 yr of age (P > 0.01). These data indicate no long-term negative effects for the use of intra-articular lipopolysaccharide as an acute inflammatory model in skeletally mature and immature horses.