我懂了:
System.Configuration.Configuration webconfig = System.Web.Configuration.WebConfigurationManager.OpenMachineConfiguration();
System.Net.Configuration.MailSettingsSectionGroup mailSection = webconfig.GetSectionGroup("system.net/mailSettings") as System.Net.Configuration.MailSettingsSectionGroup;
mailSection.Smtp.From = "[email protected]defaultmail.com";
mailSection.Smtp.Network.Host = Service.Config.SMTP_SERVER;
mailSection.Smtp.Network.Port = Service.Config.SMTP_PORT;
webconfig.Save(System.Configuration.ConfigurationSaveMode.Modified);