BACKGROUND: Betaine is an effective antioxidant and lipopolysaccharide (LPS) is an inflammatory stimulus that can disrupt the antioxidant system. However, the precise mechanisms of betaine's antioxidant activity remain undetermined. This study aimed to examine the impact of betaine on growth, antioxidant capacity, and inflammatory cytokine production in LPS-challenged goslings. In this study, 168 healthy Jiangnan White Goslings (males, 15 days old) were selected and randomly categorized into four groups. There were 7 goslings per replicate and 6 replicates for each treatment. This study employed a 2 × 2 factorial arrangement, the goslings were provided a diet containing 0% or 0.06% betaine and were injected with physiological saline or LPS. RESULTS: Subsequent analyses revealed that on day 21 of LPS treatment, there was a significant decrease in gosling's ADFI, ADG, and BW, whereas dietary betaine supplementation improved ADFI and BW in LPS-stressed individuals (p = 0.08, p = 0.09). LPS challenge significantly upregulated pro-inflammatory interleukin-1β (IL-1β) mRNA (p <
0.05), whereas betaine significantly lowered these levels (p <
0.05). During the LPS stress period (days 16-21), the superoxide dismutase (SOD) activity and total antioxidant capacity (T-AOC) were significantly reduced, while malondialdehyde (MDA) levels were increased in the liver and jejunal mucosa (p <
0.05). Betaine administration reversed these changes and significantly increased SOD and T-AOC levels while decreasing the MDA content (p <
0.05). However, both LPS and betaine did not affect the mRNA levels of SOD1 or glutathione peroxidase 4 (GSH-Px4) in the liver or jejunal mucosa during the stress (days 16-21) or recovery (days 22-28) periods. CONCLUSIONS: In summary, these analyses revealed that dietary betaine administration can effectively abrogate LPS-induced oxidative liver damage.