I believe what you have encountered is not a limitation in EPiServer Mail itself but rather a limitation set by the outbound SMTP server that you have configured.
(By the looks of it the message "552 4.3.1 message size exceeds fixed maximum message size" comes from the SMTP dialog with that server.)
I want to ask what is the maximum message size that can be send via EPiServer Mail and does it deppend in any way on configuration of EPiServer Mail, IIS or smtp on the server.
The concrete problem we are facing is that the following message has been reported several to appear in Mail tab of EPiServer in New Mailing window:
"552 4.3.1 message size exceeds fixed maximum message size episerver mail"