By using the powerful Outbound Traffic Manager, this can be done easily. Create a new policy rule, located at Network > Outbound Policy, as shown in the following illustration.
The rule says:
For any outbound SMTP traffic (TCP Port 25), use the Enforced algorithm.
Send matching traffic only to WAN1.
* This is a common requirement when your SMTP requests are accepted by a specific ISP.
What if I have two different locally hosted mail server that use two different public ip but the same WAN? How can I setup an outbound policy that mail A will send using ip A and mail B to isp B?