The results showed: (1) Neuroticism is positively related to negative affect, but negatively correlated with positive affect, self-esteem and life satisfaction. (2) Positive and negative affect were the full mediators between neuroticism and self-esteem. Self-esteem was the full mediator between positive and negative affect and life satisfaction. (3) Neuroticism couldn’t affect life satisfaction directly, only indirectly affected life satisfaction through two mediation chains. One was the positive affect-self-esteem mediation chain, the other was the negative affect-self-esteem mediation chain. Both absolute and incremental fit indices indicated that this chain type mediation model had a good fit to data. And, all latent variable variances and factor loadings were highly significant. These findings highlight the complex nature of association between neuroticism and life satisfaction. Neuroticism indirectly affects life satisfaction through the positive affect-self-esteem mediation chain and the negative affect-self-esteem mediation chain, but can’t directly affect life satisfaction. This study provides new and further evidence that neuroticism is associated with a number of negative life outcomes, including less happy, more aversive mood, poor self-esteem, low levels of life satisfaction.